Papillomaviruses (PVs) generally induce benign epithelial proliferation at the site of infection. However, there is a strong association between malignant progression of human genital lesions and certain "high risk" HPV types, most frequently HPV16. Analysis of the structural and immunogenic features of PVs has been hampered by the inability to propagate the viruses in cultured cells. To partially overcome this handicap, we have expressed the L1 major capsid proteins of several human and animal PV types via baculovirus vectors. The L1 proteins were expressed at high levels and assembled into PV virion- like structures. We have identified two HPV16 L1 clones from primary lesions that, unlike the prototype L1 used in previous studies, efficiently assembles into particles. The self assembled BPV L1 resembled intact virions in being able to induce high titer neutralizing antiserum. These results indicate that L1 has the intrinsic capacity to assemble into empty capsid-like structures whose immunogenicity is similar to infectious virions. Particles containing both L1 and the L2 minor capsid protein have also been generated. These types of particles might be considered as a candidate for a vaccine to prevent PV infection. There exists no effective serological assay to measure high risk genital HPV infection. We have developed an ELISA based on HPV16 L1/L2 particles and determined that two-thirds of women who are positive for HPV16 DNA by PCR have significant reactivity to the assembled virion proteins. Less than 10% of the sera from women negative for HPV DNA or positive for low risk HPV6 or HPV11 DNA gave positive reactions. This assay, or a similar one based on a mixture of high risk HPV particles, may aid in determining the natural history of high risk HPV infection and might be useful as an adjunct to Pap screening to identify women at risk for developing cervical cancer. We have previously reported that BPV E5 induces the ligand independent activation of growth factor receptors. Analysis of receptor chimeras has determined that the transmembrane domain of PDGFR is primarily responsible for its association with and responsiveness to E5, while the intracellular domain of EGFR is required for its association with and activation by E5. These results strongly suggest that E5 activates the two receptors by different mechanisms.